DE69710319T2 - Para-substituierte phenylpropansäure derivate als integrin-antagonisten - Google Patents
Para-substituierte phenylpropansäure derivate als integrin-antagonistenInfo
- Publication number
- DE69710319T2 DE69710319T2 DE69710319T DE69710319T DE69710319T2 DE 69710319 T2 DE69710319 T2 DE 69710319T2 DE 69710319 T DE69710319 T DE 69710319T DE 69710319 T DE69710319 T DE 69710319T DE 69710319 T2 DE69710319 T2 DE 69710319T2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- carbonyl
- phenyl
- aminoiminomethyl
- phenylalanine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 108010044426 integrins Proteins 0.000 title claims abstract description 26
- 102000006495 integrins Human genes 0.000 title claims abstract description 26
- 239000005557 antagonist Substances 0.000 title description 9
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical class OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 390
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 366
- -1 nitro, amino Chemical group 0.000 claims description 317
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 224
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 206
- 125000003118 aryl group Chemical group 0.000 claims description 135
- 125000000217 alkyl group Chemical group 0.000 claims description 105
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 92
- 229960005190 phenylalanine Drugs 0.000 claims description 85
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 74
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000001188 haloalkyl group Chemical group 0.000 claims description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 150000004702 methyl esters Chemical class 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 21
- 125000004104 aryloxy group Chemical group 0.000 claims description 21
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 229940124530 sulfonamide Drugs 0.000 claims description 18
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical group OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 17
- 150000003456 sulfonamides Chemical group 0.000 claims description 17
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- CJGXMNONHNZEQQ-JTQLQIEISA-N ethyl (2s)-2-amino-3-phenylpropanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=CC=C1 CJGXMNONHNZEQQ-JTQLQIEISA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000004494 ethyl ester group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 206010027476 Metastases Diseases 0.000 claims description 9
- 208000001132 Osteoporosis Diseases 0.000 claims description 9
- 125000004442 acylamino group Chemical group 0.000 claims description 9
- 125000003368 amide group Chemical group 0.000 claims description 9
- 230000033115 angiogenesis Effects 0.000 claims description 9
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000004995 haloalkylthio group Chemical class 0.000 claims description 9
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 230000015590 smooth muscle cell migration Effects 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 208000037147 Hypercalcaemia Diseases 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000000148 hypercalcaemia Effects 0.000 claims description 7
- 208000030915 hypercalcemia disease Diseases 0.000 claims description 7
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 7
- 230000003211 malignant effect Effects 0.000 claims description 7
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- BGOYLHDSWOZUFI-QHCPKHFHSA-N (2s)-2-(2-methylpropoxycarbonylamino)-3-[4-[[3-(3,4,5,6-tetrahydro-2h-azepin-7-ylamino)-5-(trifluoromethyl)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OCC(C)C)C(O)=O)=CC=C1NC(=O)C1=CC(NC=2CCCCCN=2)=CC(C(F)(F)F)=C1 BGOYLHDSWOZUFI-QHCPKHFHSA-N 0.000 claims description 6
- KRRQTWUJZJLGSG-IBGZPJMESA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)-5-(trifluoromethyl)benzoyl]amino]phenyl]-2-(2-methylpropoxycarbonylamino)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OCC(C)C)C(O)=O)=CC=C1NC(=O)C1=CC(N=CNN)=CC(C(F)(F)F)=C1 KRRQTWUJZJLGSG-IBGZPJMESA-N 0.000 claims description 6
- PNHCPGXDFDVBSF-SFHVURJKSA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1NC(=O)C1=CC=CC(NC=NN)=C1 PNHCPGXDFDVBSF-SFHVURJKSA-N 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- QPLWLOWSRGOOEW-QHCPKHFHSA-N (2s)-2-(butylsulfonylamino)-3-[4-[[3-(3,4,5,6-tetrahydro-2h-azepin-7-ylamino)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1NC(=O)C1=CC=CC(NC=2CCCCCN=2)=C1 QPLWLOWSRGOOEW-QHCPKHFHSA-N 0.000 claims description 5
- UTVUPRALEHQTEG-KRWDZBQOSA-N (2s)-2-acetamido-3-[4-[[3-(hydrazinylmethylideneamino)phenyl]carbamoylamino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)C)C(O)=O)=CC=C1NC(=O)NC1=CC=CC(N=CNN)=C1 UTVUPRALEHQTEG-KRWDZBQOSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 5
- JOAFADWNCSAUPV-QHCPKHFHSA-N (2s)-2-(butylsulfonylamino)-3-[4-[[3-(3,4,5,6-tetrahydro-2h-azepin-7-ylamino)-5-(trifluoromethyl)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1NC(=O)C1=CC(NC=2CCCCCN=2)=CC(C(F)(F)F)=C1 JOAFADWNCSAUPV-QHCPKHFHSA-N 0.000 claims description 4
- HYEZGGXSGXCKPJ-IBGZPJMESA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-(2-methylpropoxycarbonylamino)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OCC(C)C)C(O)=O)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 HYEZGGXSGXCKPJ-IBGZPJMESA-N 0.000 claims description 4
- USNUTJBKWWWSSX-UHFFFAOYSA-N 3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]propanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=CC(CCC(O)=O)=CC=2)=C1 USNUTJBKWWWSSX-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- KKWYGXHIOVCJJL-UHFFFAOYSA-N ethyl 3-[4-[[3-(n'-hydroxycarbamimidoyl)benzoyl]amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1NC(=O)C1=CC=CC(C(N)=NO)=C1 KKWYGXHIOVCJJL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- 235000000346 sugar Nutrition 0.000 claims description 4
- 150000008163 sugars Chemical class 0.000 claims description 4
- RBYQPKHTSHEEQK-IBGZPJMESA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)-5-(trifluoromethyl)benzoyl]amino]phenyl]-2-(3-methylbutanoylamino)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)CC(C)C)C(O)=O)=CC=C1NC(=O)C1=CC(N=CNN)=CC(C(F)(F)F)=C1 RBYQPKHTSHEEQK-IBGZPJMESA-N 0.000 claims description 3
- UCALCLSMHHIHRW-INIZCTEOSA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-(methoxycarbonylamino)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC)C(O)=O)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 UCALCLSMHHIHRW-INIZCTEOSA-N 0.000 claims description 3
- UNOORXNLEMQEPL-UHFFFAOYSA-N 2-(2-carboxyethyl)-5-[[3-(hydrazinylmethylideneamino)benzoyl]amino]benzoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=C(C(CCC(O)=O)=CC=2)C(O)=O)=C1 UNOORXNLEMQEPL-UHFFFAOYSA-N 0.000 claims description 3
- DLNOKNUYRAJBAU-UHFFFAOYSA-N 2-[[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]methyl]butanoic acid Chemical compound C1=CC(CC(CC)C(O)=O)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 DLNOKNUYRAJBAU-UHFFFAOYSA-N 0.000 claims description 3
- LOYHYBIVXDMARE-UHFFFAOYSA-N 3-[4-[(3-methanehydrazonoylbenzoyl)amino]phenyl]propanoic acid Chemical compound NN=CC1=CC=CC(C(=O)NC=2C=CC(CCC(O)=O)=CC=2)=C1 LOYHYBIVXDMARE-UHFFFAOYSA-N 0.000 claims description 3
- HYVQLWARYNMRQD-UHFFFAOYSA-N 3-[4-[[3-(carbamoylamino)benzoyl]amino]phenyl]propanoic acid Chemical compound NC(=O)NC1=CC=CC(C(=O)NC=2C=CC(CCC(O)=O)=CC=2)=C1 HYVQLWARYNMRQD-UHFFFAOYSA-N 0.000 claims description 3
- AARFVOIDVCDXLK-UHFFFAOYSA-N 3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]-3-hydroxyphenyl]propanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C(=CC(CCC(O)=O)=CC=2)O)=C1 AARFVOIDVCDXLK-UHFFFAOYSA-N 0.000 claims description 3
- LEMCQRKZYNMBJH-UHFFFAOYSA-N 3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-3-phenylpropanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=CC(=CC=2)C(CC(O)=O)C=2C=CC=CC=2)=C1 LEMCQRKZYNMBJH-UHFFFAOYSA-N 0.000 claims description 3
- HPHWFFAHBLPFEK-UHFFFAOYSA-N 3-[4-[[3-(hydrazinylmethylideneamino)phenyl]sulfonylamino]phenyl]propanoic acid Chemical compound NNC=NC1=CC=CC(S(=O)(=O)NC=2C=CC(CCC(O)=O)=CC=2)=C1 HPHWFFAHBLPFEK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- FVYPQUPVQDBRPJ-UHFFFAOYSA-N ethyl 3-[4-[[3-(carbamoylamino)benzoyl]amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1NC(=O)C1=CC=CC(NC(N)=O)=C1 FVYPQUPVQDBRPJ-UHFFFAOYSA-N 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- DHURYRPQAWBJLB-IBGZPJMESA-N (2s)-2-(butylsulfonylamino)-3-[4-[[3-(hydrazinylmethylideneamino)-5-(trifluoromethyl)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1NC(=O)C1=CC(N=CNN)=CC(C(F)(F)F)=C1 DHURYRPQAWBJLB-IBGZPJMESA-N 0.000 claims description 2
- SLYHQGMHAQXNGT-HNNXBMFYSA-N (2s)-2-amino-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]propanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=CC(C[C@H](N)C(O)=O)=CC=2)=C1 SLYHQGMHAQXNGT-HNNXBMFYSA-N 0.000 claims description 2
- XFNSENZQCHMFHQ-INIZCTEOSA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-(methanesulfonamido)propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)C)C(O)=O)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 XFNSENZQCHMFHQ-INIZCTEOSA-N 0.000 claims description 2
- ZVLVYKCGPSZKTH-SFHVURJKSA-N (2s)-3-[4-[[3-(hydrazinylmethylidenecarbamoyl)benzoyl]amino]phenyl]-2-(propan-2-yloxycarbonylamino)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)C)C(O)=O)=CC=C1NC(=O)C1=CC=CC(C(=O)N=CNN)=C1 ZVLVYKCGPSZKTH-SFHVURJKSA-N 0.000 claims description 2
- GPNNVIVBATZBGX-UHFFFAOYSA-N 2-(2-carboxyethyl)-5-[[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)benzoyl]amino]benzoic acid Chemical compound C1=C(C(O)=O)C(CCC(=O)O)=CC=C1NC(=O)C1=CC=CC(NC=2NCCCN=2)=C1 GPNNVIVBATZBGX-UHFFFAOYSA-N 0.000 claims description 2
- YFSSRHIMVAXZMH-UHFFFAOYSA-N 2-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]butanedioic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=CC(=CC=2)C(CC(O)=O)C(O)=O)=C1 YFSSRHIMVAXZMH-UHFFFAOYSA-N 0.000 claims description 2
- NWAXONRVNDSNGG-UHFFFAOYSA-N 3-[2-(dimethylamino)-4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(N(C)C)=CC(NC(=O)C=2C=C(C=CC=2)N=CNN)=C1 NWAXONRVNDSNGG-UHFFFAOYSA-N 0.000 claims description 2
- WHVNOCXIIATORN-UHFFFAOYSA-N 3-[3-[[[3-(carbamoylamino)benzoyl]amino]methyl]phenyl]propanoic acid Chemical compound NC(=O)NC1=CC=CC(C(=O)NCC=2C=C(CCC(O)=O)C=CC=2)=C1 WHVNOCXIIATORN-UHFFFAOYSA-N 0.000 claims description 2
- OMSLLPXFSXEYMG-UHFFFAOYSA-N 3-[4-[[(3-methanehydrazonoylbenzoyl)amino]methyl]phenyl]propanoic acid Chemical compound NN=CC1=CC=CC(C(=O)NCC=2C=CC(CCC(O)=O)=CC=2)=C1 OMSLLPXFSXEYMG-UHFFFAOYSA-N 0.000 claims description 2
- OYDUIDMZDZUPGH-UHFFFAOYSA-N 3-[4-[[3-(benzylcarbamoylamino)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1NC(=O)C1=CC=CC(NC(=O)NCC=2C=CC=CC=2)=C1 OYDUIDMZDZUPGH-UHFFFAOYSA-N 0.000 claims description 2
- ZSKDVLPPYBUVTL-UHFFFAOYSA-N 3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]butanoic acid Chemical compound C1=CC(C(CC(O)=O)C)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 ZSKDVLPPYBUVTL-UHFFFAOYSA-N 0.000 claims description 2
- YXJXRVJNCWQQCZ-UHFFFAOYSA-N 4-(carboxymethylamino)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-4-oxobutanoic acid Chemical compound NN=CNC1=CC=CC(C(=O)NC=2C=CC(=CC=2)C(CC(O)=O)C(=O)NCC(O)=O)=C1 YXJXRVJNCWQQCZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- YQJINDVRPMYQRX-FQEVSTJZSA-N ethyl (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-(propan-2-yloxycarbonylamino)propanoate Chemical compound C1=CC(C[C@@H](C(=O)OCC)NC(=O)OC(C)C)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 YQJINDVRPMYQRX-FQEVSTJZSA-N 0.000 claims description 2
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims description 2
- 229960005137 succinic acid Drugs 0.000 claims description 2
- QHSSKTAHDJTGGJ-UHFFFAOYSA-N tert-butyl 3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]-3-hydroxyphenyl]propanoate Chemical compound OC1=CC(CCC(=O)OC(C)(C)C)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 QHSSKTAHDJTGGJ-UHFFFAOYSA-N 0.000 claims description 2
- SHIVUZBHDSTXNM-IBGZPJMESA-N (2s)-2-(butylsulfonylamino)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1NC(=O)C1=CC=CC(N=CNN)=C1 SHIVUZBHDSTXNM-IBGZPJMESA-N 0.000 claims 2
- LMAYIJYGWKNYGE-IBGZPJMESA-N (2s)-3-[4-[[3-(hydrazinylmethylideneamino)benzoyl]amino]phenyl]-2-(morpholine-4-carbonylamino)propanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC=2C=CC(C[C@H](NC(=O)N3CCOCC3)C(O)=O)=CC=2)=C1 LMAYIJYGWKNYGE-IBGZPJMESA-N 0.000 claims 2
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- VSEYYEKRZNRECT-UHFFFAOYSA-N methyl 2-bromo-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC=C1Br VSEYYEKRZNRECT-UHFFFAOYSA-N 0.000 description 1
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- LOCJPOYKBUUVKU-UHFFFAOYSA-N methyl 3-amino-4-chlorobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C(N)=C1 LOCJPOYKBUUVKU-UHFFFAOYSA-N 0.000 description 1
- VZDNXXPBYLGWOS-UHFFFAOYSA-N methyl 3-aminobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1 VZDNXXPBYLGWOS-UHFFFAOYSA-N 0.000 description 1
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- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 239000008363 phosphate buffer Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
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- CEEVRMDYKKNRAW-UHFFFAOYSA-N pyrazine-2-carboximidamide Chemical compound NC(=N)C1=CN=CC=N1 CEEVRMDYKKNRAW-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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- 230000032258 transport Effects 0.000 description 1
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- 150000003852 triazoles Chemical class 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/22—Y being a hydrogen or a carbon atom, e.g. benzoylguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/28—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to cyano groups, e.g. cyanoguanidines, dicyandiamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/52—Y being a hetero atom
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/14—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to said nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1428896P | 1996-03-29 | 1996-03-29 | |
PCT/US1997/004460 WO1997036859A1 (en) | 1996-03-29 | 1997-03-26 | Para-substituted phenylpropanoic acid derivatives as integrin antagonists |
Publications (2)
Publication Number | Publication Date |
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DE69710319D1 DE69710319D1 (de) | 2002-03-21 |
DE69710319T2 true DE69710319T2 (de) | 2002-08-14 |
Family
ID=21764580
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69710319T Expired - Fee Related DE69710319T2 (de) | 1996-03-29 | 1997-03-26 | Para-substituierte phenylpropansäure derivate als integrin-antagonisten |
Country Status (12)
Country | Link |
---|---|
US (2) | US5952381A (ja) |
EP (1) | EP0891325B1 (ja) |
JP (1) | JP2000515493A (ja) |
AT (1) | ATE212978T1 (ja) |
AU (1) | AU2536097A (ja) |
CA (1) | CA2250698A1 (ja) |
DE (1) | DE69710319T2 (ja) |
DK (1) | DK0891325T3 (ja) |
ES (1) | ES2172780T3 (ja) |
HK (1) | HK1044527A1 (ja) |
PT (1) | PT891325E (ja) |
WO (1) | WO1997036859A1 (ja) |
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GB9811969D0 (en) | 1998-06-03 | 1998-07-29 | Celltech Therapeutics Ltd | Chemical compounds |
GB9812088D0 (en) | 1998-06-05 | 1998-08-05 | Celltech Therapeutics Ltd | Chemical compounds |
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GB9821222D0 (en) | 1998-09-30 | 1998-11-25 | Celltech Therapeutics Ltd | Chemical compounds |
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KR20010086112A (ko) * | 1998-12-16 | 2001-09-07 | 빌프리더 하이더 | 인테그린 길항제로서의 신규한 비페닐 및 비페닐 유사화합물 |
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JP2002533387A (ja) | 1998-12-23 | 2002-10-08 | ジー.ディー.サール & カンパニー | 腫瘍治療の複合療法としてインテグリン拮抗物質と一つ以上の抗腫瘍剤を使用する方法 |
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AU2004249120B2 (en) * | 2003-05-23 | 2008-07-24 | Glaxosmithkline | Guanidino-substituted quinazolinone compounds as MC4-R agonists |
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MXPA06005736A (es) * | 2003-11-19 | 2006-12-14 | Chiron Corp | Compuestos de quinazolinona con bioacumulacion reducida. |
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US20140010783A1 (en) * | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
ES2647585T3 (es) | 2012-07-18 | 2017-12-22 | Saint Louis University | Derivados de aminoácido beta como antagonistas de integrina |
US8716226B2 (en) | 2012-07-18 | 2014-05-06 | Saint Louis University | 3,5 phenyl-substituted beta amino acid derivatives as integrin antagonists |
AU2016381336A1 (en) | 2015-12-30 | 2018-06-28 | Saint Louis University | Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists |
CN107652210B (zh) * | 2017-09-30 | 2021-01-01 | 瑞阳(上海)新药研发有限公司 | 一种胍类化合物或其药学上可接受的盐、其制备方法和应用 |
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FI890918A (fi) * | 1988-03-11 | 1989-09-12 | Eisai Co Ltd | Polypeptider. |
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WO1993008823A1 (en) * | 1991-11-06 | 1993-05-13 | Tanabe Seiyaku Co., Ltd. | Guanidinyl and related cell adhesion modulation compounds |
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ATE227567T1 (de) * | 1994-05-27 | 2002-11-15 | Merck & Co Inc | Präparate zur hemmung der durch osteoklasten vermittelten knochenresorption |
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1997
- 1997-03-26 EP EP97916852A patent/EP0891325B1/en not_active Expired - Lifetime
- 1997-03-26 WO PCT/US1997/004460 patent/WO1997036859A1/en active IP Right Grant
- 1997-03-26 CA CA002250698A patent/CA2250698A1/en not_active Abandoned
- 1997-03-26 DK DK97916852T patent/DK0891325T3/da active
- 1997-03-26 AT AT97916852T patent/ATE212978T1/de not_active IP Right Cessation
- 1997-03-26 DE DE69710319T patent/DE69710319T2/de not_active Expired - Fee Related
- 1997-03-26 ES ES97916852T patent/ES2172780T3/es not_active Expired - Lifetime
- 1997-03-26 JP JP09535308A patent/JP2000515493A/ja not_active Ceased
- 1997-03-26 PT PT97916852T patent/PT891325E/pt unknown
- 1997-03-26 AU AU25360/97A patent/AU2536097A/en not_active Abandoned
- 1997-03-27 US US08/826,244 patent/US5952381A/en not_active Expired - Fee Related
-
1999
- 1999-04-08 US US09/288,742 patent/US6251944B1/en not_active Expired - Fee Related
-
2002
- 2002-05-28 HK HK02103989.5A patent/HK1044527A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
WO1997036859A1 (en) | 1997-10-09 |
EP0891325B1 (en) | 2002-02-06 |
DE69710319D1 (de) | 2002-03-21 |
CA2250698A1 (en) | 1997-10-09 |
US6251944B1 (en) | 2001-06-26 |
HK1044527A1 (zh) | 2002-10-25 |
DK0891325T3 (da) | 2002-05-21 |
PT891325E (pt) | 2002-07-31 |
AU2536097A (en) | 1997-10-22 |
JP2000515493A (ja) | 2000-11-21 |
US5952381A (en) | 1999-09-14 |
ATE212978T1 (de) | 2002-02-15 |
EP0891325A1 (en) | 1999-01-20 |
ES2172780T3 (es) | 2002-10-01 |
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